The purpose of the proposed research is to investigate the response of catecholamine and acetylcholine-mediated alterations in the metabolism of specific structures in brain, including alterations in cyclic nucleotide and proteosynthesis in the development of tolerance and persistence of long term drug sensitivity in abstinent animals. The specific aims are: 1. To characterize the response of cyclic nucleotides to acute and chronic morphine treatment, in specific brain regions. 2. To determine the contribution of catecholamines and acetylcholine in mediating these region specific alterations. 3. To systematically assess the alterations in brain region genomic transcription resulting from morphine treatment. 4. To determine the relatedness of transcriptional alterations occurring in the acute state to those in the chronic tolerant and abstinent state. 5. To assess the probability that transcriptional alterations may result in qualitative, region specific changes in protein synthesis.